We hypothesized that treatment with high dose acyclovir would decrease mortality and morbidity of CNS or disseminated neonatal herpes simplex virus infection both acutely and long-term. This trial is a randomized, double-blind controlled clinical trial utilizing high dose acyclovir Vs. standard vidarabine therapy. Patients will be treated in the GCRC for twenty-one consecutive days and then intermittently from day 28 through 6 months. Laboratory work including spinal tap for CSF fluid will be done on days 1 and 21. CT will be done on days 1 and 21 with other CTs as medically indicated. Follow-up out-patient visits will be at 1, 2, 3 and 4 years and will include neurological and developmental assessments. During the first phase of the study, 16 babies nation-wide were enrolled at a dosage of 45mg/kg/day. There was no evidence of toxicity at this doseage; thus, medication doseage was escalated to 60mg/kg/day. A total of 72 patients have been enrolled at the 60mg/kg/day dose at all centers. No new patients have been enrolled at UAB this year; 3 outptaient visits were recorded for follow-up.